The compounds having oxirane ring (epoxides) are important targets in organic synthesis, since many of them themselves have biologically active. The oxirane ring in epoxide can be easily substituted by other functional groups, and therefore the epoxides are useful substances which can be employed as starting materials or intermediates for organic synthesis.
Synthesis of such epoxides is carried out through the reaction for formation of oxirane rings. The method for formation of an oxirane ring can contain, for example, the following reactions:
(i) The reaction involving oxidization of the double bond of olefin with peroxides; and PA1 (ii) The nucleophilic substitution reaction between hydroxide groups adjacent to each other.
An example of the reaction (i) is the oxidative addition reaction (prileschajew reaction) by using peracids such as perbenzoic acid, m-chloroperbenzoic acid, and peracetic acid, as shown in equation 1 below, and another example is Scharpless oxidation in which an allyl alcohol is reacted with an appropriate oxidizing agent in the presence of metal catalyst to stereoselectively give an epoxide, as shown in equation 2 below. ##STR5## where R.sup.6, R.sup.7, R.sup.8, and R.sup.9 represent a hydrogen atom, an alkyl group, an alkenyl group, an aryl group, an alkoxy group, an aryloxy group, an acyl group, an alkyloxycarbonyl group, an aryloxycarbonyl group, an aralkyl group, a silyl group, and a silyloxy group; the groups may be bonded with each other to form rings in the case where these groups can be bivalent; and these groups may be the same or different, may contain substituting groups, or may be branched. R represents an alkyl group, an aryl group or an acyl group. ##STR6## where R.sup.6, R.sup.7, R.sup.8, and R.sup.9 are defined as above, and Cat. represents a metal complex catalyst containing a metal such as vanadium, molybdenum, or titanium.
An example of the reaction (ii) is that as shown in the following equation 3. More specifically, a diol is introduced to the double bond of olefin to form a trans-isomer. Then, a leaving group is introduced to one of the two hydroxyl groups, and then the other hydroxyl group is subjected to the intramolecular nucleophilic substitution reaction, thereby forming a oxirane. ##STR7## where R.sup.6, R.sup.7, R.sup.8, and R.sup.9 are the same as defined as above; and R.sup.10 is a protecting group for a hydroxyl group, which can be released as R.sup.10 O--, for example, a acyl group.
In the synthesis of an epoxide, the stereochemistry of the oxirane ring introduced to the double bond is important. In a chain (open ring) type olefin, the conversion of the double bond of the olefin to oxirane ring can be formed an epoxide which can produce two possible diols of threo or erythro isomers after the epoxide is hydrolyzed, depending on the direction of approach of an oxidizing agent such as peracids to double bond plane. Also, in the case of a cyclic compound, two possible isomers can be obtained. These isomers can be formed depending on the direction of approach of an oxidizing agent to the ring plane.
Thus, the stereoselectivity between these isomers, and the control of the selectivity are of the great importance. Particular, it is difficult, with the conventional technique, to form an oxirane ring selectively on the more sterically hindered side of the double bond.
For example, in the reaction (i) for preparing an oxirane ring by use of peroxide, since the peroxide approaches to the less hindered side, an oxirane ring is formed on that side. Therefore, it is difficult to obtain the other isomer having an oxirane ring on the more sterically hindered side. In the case of oxidization of the double bond of a cyclic allyl alcohol, the peroxide is attracted to the hydroxyl group by the hydrogen bonding of the peroxide to the hydroxyl group, and therefore the hydroxyl group at the allyl position is not the steric hindrance. Accordingly, an oxirane ring is formed on the more sterically hindered side of the double bond. In the case of sharpless oxidation using a metal catalyst, the selectivity is higher than that of the reaction (i), and therefore one of the isomers of the epoxide, which produce the diol compound of the threo-isomer after hydrolysis, is preferentially obtained. However, in this method, if there is a substituting group which is a steric hindrance on the same side as the hydroxyl group, a peroxide or metal catalyst cannot approach to the compound from the side where the hydroxyl group is present. As a result, this method has such a problem that the selectivity is lowered, the reaction does not proceed, or the starting material is decomposed. Further, this method suffers from the defect that it can be applied only to allyl alcohol.
With the method of forming an oxirane ring through the nucleophilic substitution reaction between adjacent hydroxyl groups in the diol which are trans form as in the reaction (ii), in order to obtain an epoxide having the desired configuration, the two hydroxyl groups must be arranged at the trans-position, and therefore the two hydroxyl groups must be stereoselectively introduced to the double bond of olefin in a trans form. Further, in some cases, it is necessary to introduce a leaving group regioselectively to one of the two hydroxyl groups and the control of the regioselectivity is difficult.
As described above, with the conventional methods, it is difficult to form an oxirane ring selectively on the more sterically hindered side of the double bond of olefin.
In the meantime, as mentioned before, epoxides are important compounds in synthetic chemistry. Of the epoxides, 1,6:3,4-dianhydro-.beta.-D-talopyranose (1c), in particular, is used as a synthetic intermediate for a sugar compound or sugar-containing compound which is focused as a useful biologically active substance in the field of fine chemicals such as medicine and pesticides, and the utility of the compound as a starting material is expected in the future. ##STR8##
Further, the compound (1c) is of a great importance as a synthetic intermediate of a useful antibiotics, sibiromycin (M. Georges and D. MacKay, Carbohydr. Res., 130, 115 (1984)). Furthermore, the compound (1c) can be converted into an endogenous feeding promoter substance, (2S, 4S)-2-hydroxy-4-hydroxymethyl-4-butanolide (3-DPA-lactone), through oxidization of the hydroxyl group, reductive cleavage of the oxirane ring, and Baeyer-Villigar oxidation. Furthermore, the compound can be easily converted into various types of deoxy sugars such as deoxymannose derivative and deoxyaminomannose derivative, and further into the constitutional unit of various useful saccharides, and sialic acid derivatives. However, the compound (1c) is a type containing an oxirane ring on the more sterically hindered side of the ring, and the synthesis of the compound has been difficult as mentioned above. Therefore, the development of the method of synthesizing the compound (1c) useful as a synthetic intermediate at a high efficiency is not only important in synthetic chemistry, but also significant in development of medicine and pesticides.
Conventionally, there is known a method of preparing the compound (1c), in which the compound is synthesized through a D-mannosane derivative by thermolysis of an endosperm of an ivory palm (A. E. Knauf, R. M. Hann and C. S. Hudson, J. Am. Chem. Soc., 63, 1447 (1941), R. M. Hann and C. S. Hudson, J. Am. Chem. Soc., 64, 925 (1942)).
However, the conventional method involves five steps, and the yield of the product is as low as 5%; therefore is not fully satisfactory in the number of steps, and the yield.